POS0821 DIFFERENTIALLY EXPRESSED GENES (DEGS) OVERLAPPED FROM DATASETS FROM PATIENTS WITH SJÖGREN’S SYNDROME (SS) THROUGH INTEGRATIVE BIOINFORMATICS ANALYSIS DISPLAY INTERFERON SIGNATURE
Authors: R. Martinez, M. Gelinas Martin del Campo, C. Elizondo Solis, A. Montoya Rosales, M. Salinas Carmona, N. Macias-Segura
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Sjögren's Syndrome is an autoimmune disease comprised by oral and ocular dryness due to destruction of lacrimal and salivary glands. It may be associated with other rheumatological pathologies such as Rheumatoid Arthritis or Systemic Lupus Erythematosus [1]. Bioinformatics has been used to elucidate the pathophysiology underlying rheumatological diseases [2]. Key findings include an Interferon (IFN) signature common to rheumatic diseases and aberrant activation of B and T cells [3]. Nonetheless, they are inconclusive since several studies propose different DEGs. <h3>Objectives</h3> We aimed to identify overlapped genes across datasets of gene expression from patients with primary SS doing an integrative bioinformatics metanalysis. <h3>Methods</h3> A search strategy was designed in the Gene Expression Omnibus platform to identify datasets of gene expression profiling by array experiments in patients with SS. The inclusion criteria were: 1) Assays performed in humans, 2) Inclusion of healthy controls in each dataset, and 3) Data analysis with GEO2R. The exclusion criteria were: 1) Incomplete information of the genes, and 2) Gene expression by RNAseq. DEGs were selected when p &lt; 0.05 and log fold change &gt; 2 or &lt; -2. Functional enrichment analysis was realized with free-access platforms GeneMania and DAVID from the significant overlapped genes. A protein-protein interaction (PPI) analysis was constructed with STRING. A topologic interaction network using CytoHubba to find the genes with the highest interaction within the cluster was realized. <h3>Results</h3> 8 datasets qualified to be analyzed. 260 DEGs were identified. 10 DEGs overlapped among the datasets. Prediction analysis yielded 21 co-expressed pairs. Functional enrichment analysis showed 3 biological processes in which those genes participate (Table 1): 20 genes in defense response to virus, 14 in response to virus, and 10 in the negative regulation of the viral genome replication. Most of them belong to the type I IFN signature. PPI analysis showed a cluster of 27 genes and the topological analysis yielded 10 genes (Figure 1). <h3>Conclusion</h3> We identified DEGs through bioinformatic and functional enrichment analysis. 10 genes appeared in different datasets, while 21 were listed as their co-expressed pairs. These genes play a fundamental role in the processes of Defense response to virus, Response to virus and Negative regulation of the viral genome replication. Most of them belong to the type I IFN signature. An in vivo analysis in patients with primary SS is needed to validate these genes as possible diagnostic biomarkers and even possible therapeutic targets. <h3>References</h3> [1]Bjordal, O., Norheim, K. B., Rødahl, E., Jonsson, R., &amp; Omdal, R. (2020). Primary Sjögren's syndrome and the eye. Survey of Ophthalmology, 65(2), 119–132. https://doi.org/10.1016/j.survophthal.2019.10.004 [2]Li, N., Li, L., Wu, M., Li, Y., Yang, J., Wu, Y., Xu, H., Luo, D., Gao, Y., Fei, X., &amp; Jiang, L. (2021). Integrated Bioinformatics and Validation Reveal Potential Biomarkers Associated With Progression of Primary Sjögren's Syndrome. Frontiers in Immunology, 12, 697157. https://doi.org/10.3389/fimmu.2021.697157 [3]Teruel, M., Barturen, G., Martínez-Bueno, M., Castellini-Pérez, O., Barroso-Gil, M., Povedano, E., Kerick, M., Català-Moll, F., Makowska, Z., Buttgereit, A., Pers, J.-O., Marañón, C., Ballestar, E., Martin, J., Carnero-Montoro, E., &amp; Alarcón-Riquelme, M. E. (2021). Integrative epigenomics in Sjögren´s syndrome reveals novel pathways and a strong interaction between the HLA, autoantibodies and the interferon signature. Scientific Reports, 11(1), 23292. https://doi.org/10.1038/s41598-021-01324-0 <h3>Disclosure of Interests</h3> None Declared.